Our previous studies have suggested that mitochondrial dysfunction causes oxidative genomic DNA damage and contributes to tumorigenesis. A major contributing factor is ambient oxygen which is the essential substrate for reactive oxygen species generation that can cause biological damage. Environmental and genetic methods will be used to modulate redox homeostasis and to determine their effect on energy metabolism, tumorigenesis, and cardiovascular disease. We are examining adaptive mechanisms by which cells of neoplastic or cardiovascular origin survive under oxidative or other toxic stress conditions.